Saliva is an important diagnostic fluid that has the potential to be used for detection of essential biomarkers for both oral and systemic diseases. Unfortunately, the current lack of reliable detection methods for measurement of important analytes within this complex biomatrix has hindered progress in salivary diagnostics. To help remove this barrier, recent promising activities have been initiated in microfluidic-based Lab-on-a-Chip (LOG) systems. While several miniaturized platforms are being developed now, few of these systems have evolved to the point where important protein biomarkers can be measured over the physiological range using real saliva samples. Towards this essential goal, the team of investigators from UT and UK have developed and documented carefully an integrated biochip assay system that is suitable for measurement of panels of important inflammatory markers (e.g.CRP, IL-1beta, MMP-8, TNF-alpha, IL-6)in saliva. This newly fashioned ultra-sensitive method has been used to extend saliva-based diagnostics to the low levels of CRP found in saliva, therefore allowing for the first comparison of CRP levels between healthy, periodontitis, and edentulous patients. The miniaturized system correlates nicely with established macroscopic "gold standard" methods. Thus, it now important to take the next steps to combine these functional components and associated methodologies so as to create a flexible platform system that may be used to promote and expand the field of salivary diagnostics. This U01 renewal program targets the development of portable devices that can be used to complete salivary diagnostic tests. The program will evolve with important biochip, analyzer and immunoassay development milestones to be completed in the first two years of the program. In year 1, integrated biochips and analyzers will be developed and tested. These alpha prototypes will be used to define specifications for more final systems. In year 2, fully developed biochips and analyzer suitable to serve, as beta prototypes will be fashioned. These highly functional portable systems will be used in years 3-5 to complete pre-clinical testing and validation. Salivary biomarker fingerprints that our team has already defined will be used to 1) discriminate stages of periodontitis and 2) identify risk for future cardiac events in coronary artery disease patients. Final data acquisition and FDA approval will be completed by year 5. PERFORMANCE SITE(S) (organization, city, state) University of Texas at Austin, Austin, Texas The University of Kentucky, Lexington, Kentucky The University of Louisville, Louisville, Kentucky The University of Texas Health Center at San Antonio, San Antonio, Texas PHS 398(Rev. 09/04) Page 2 Form Page 2 Principal Investigator/Program Director (Last,First, Middle): McDevitt, John T KEY PERSONNEL. See instructions. Use continuation pages as needed to providethe required information in the format shownbelow. Start with Principal Investigator. List all other key personnel in alphabetical order, last namefirst. Name eRA Commons User Name Organization Role on Project McDevitt, John University of Texas PI Anslyn, Eric University of Texas Co-l Christodoulides, Nick University of Texas Senior Researcher Ebersole, Jeff University of Kentucky Co-l Floriano, Pierre University of Texas Senior Researcher Hill Margaret University of Louisville Co-l Kinane, Denis University of Louisville Co-l Michael-Ballard, Karri University of Texas Senior Researcher Miller, Craig University of Kentucky Co-l Neikirk, Dean University of Texas Co-l Novak, M. John University of Kentucky Co-l OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Phil Fox,PhD Private Consultant Larry Fox,PhD LabNow Collaborator Human Embryonic Stem Cells El No Q Yes If the proposed project involveshuman embryonic stem cells, list below the registrationnumberof the specific cell line(s) from the following list: http://stemcells.nih.gov/reqistrv/index.asD. use continuation pages as needed. If a specific line cannot be referenced at this time, include a statement that one from the Registry will be used. Cell Line Disclosure Permission Statement. Applicable to SBIR/STTR Only. See SBIR/STTR instructions. I Yes No PHS 398 (Rev. 09/04) Page 3. Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, First,): McDevjtt, J6hh T. [unreadable][unreadable]',. : ';[unreadable].,'[unreadable][unreadable] Name eRA Commons Name Organization Role Gates, Thomas UTHSCS Co-l Redding, Spencer UTHSCS Co-l Romanovicz, Dwight *[unreadable] University of Texas Sr. Researcher Shear, Jason University of Texas Co-l Yeh, Chih-Ko UTHSCS Co-l PHS 398/2590 (Rev. 09/04) Page 4 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): McDevitt, John T. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, Performance Sites, Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells Table of Contents Detailed Budget for Initial Budget Period (or Modular Budget) Budget for Entire Proposed Period of Support (not applicable with Modular Budget) Budgets Pertaining to Consortium/Contractual Arrangements (not applicable with Modular Budget) 17 Biographical Sketch - Principal Investigator/Program Director (Not toexceed four pages) 30 Other Biographical Sketches (Not to exceed four pages for each - Seeinstructions) 34 Resources 91 Research Plan 108 Introduction to Revised Application (Not to exceed 3pages;SBIR/STTR Phase I notto exceed 1 page.) Introduction to Supplemental Application (Not to exceed one page) A. Specific Aims 108 B. Background and Significance 110 C. Preliminary Studies/Progress Report/ ^. (Items A-D: not to exceed 25 pages*) 114 Phase I Progress Report (SBIR/STTR Phase IIONLY) | * SBIR/STTR Phase I: Items A-Dlimitedto 15 pages D. Research Design and Methods 120 E. Human Subjects Research 143 Protection of Human Subjects (Required if Item 4 on the Face Page is marked "Yes") 143 Data and Safety Monitoring Plan (Required if Item 4 on the Face Page is marked "Yes" and a Phase I, II, or III clinical trial is proposed) 145 Inclusion of Women and Minorities (Required if Item 4 on the Face Page is marked "Yes" and is Clinical Research) 144 Targeted/Planned Enrollment Table (for new and continuing clinical research studies) 146 Inclusion of Children (Required if Item 4 on the Face Page is marked "Yes") 144 F. Vertebrate Animals 145 G. Literature Cited 149 H. Consortium/Contractual Arrangements 155 I. Resource Sharing 161 J. Letters of Support (e.g., Consultants) 169 Commercialization Plan (SBIR/STTR Phase II and Fast-Track ONLY) Checklist. 173 Appendix (Five collatedsets. Nopage numbering necessary for Appendix.) Check if Appendix is Appendices NOT PERMITTED for Phase I SBIR/STTR unless specifically solicited.... Included Number of publications and manuscripts accepted for publication (not to exceed 10) Other items (list): Appendix Tasks and milestones Abbreviations Seven relevant publications PHS 398 (Rev. 09/04) Page 5 Form Page 3